The major objective of this research is to delineate the role of cell-mediated immune mechanisms in pernicious anemia. This disease is thought to be immunologically induced and genetically determined; and patients with pernicious anemia have an increased risk of developing gastric carcinoma. Thus, an inherited derangement in immune responsiveness appears to induce organ-specific disease and is related to malignant transformation. The role of the lymphocyte in pernicious anemia takes on particular importance since most autoimmune diseases are induced by cell-mediated immune phenomena and one of the major functions of lymphocytes is their ability to recognize and destroy neoplastic cells. The response of lymphocytes (from patients with pernicious anemia) to gastric antigens should give considerable information regarding the pathogenetic mechanisms operative in this disorder. Moreover, qualitative and/or quantitative differences in lymphocyte response to various gastric antigens may relate immunologic responsiveness to the presence or risk of developing gastric carcinoma. The overall aim is to gain insight into the relationship between lymphocyte-mediated immune mechanisms, organ-specific disease and malignant transformation in pernicious anemia.